Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Neurovascular Research
  4. Volume 21, Issue 2
  5. Article
Volume 21, Issue 2
  • ISSN: 1567-2026
  • E-ISSN: 1875-5739

Abstract

Background

Previous studies on transcriptional profiles suggested dysregulation of multiple RNA species in Alzheimer’s disease. However, despite recent investigations revealing various aspects of circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) networks in Alzheimer's Disease (AD) pathogenesis, few genome-wide studies have explored circRNA-associated profiles in AD patients exhibiting varying degrees of cognitive loss.

Objective

To investigate the potential pathogenesis-related molecular biological changes in the various stages of AD progression.

Methods

Whole transcriptome sequencing was performed on the peripheral blood of 7 normal cognition (NC) subjects, 8 patients with mild cognitive impairment, 8 AD patients with mild dementia (miD), and 7 AD patients with moderate dementia (moD). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to predict the potential functions of the maternal genes of microRNAs (miRNAs), circRNAs and long non-coding RNAs (lncRNAs). The construction of ceRNA network was performed between the NC group and each diseased group based on the differently expressed RNAs.

Results

In total, 3568 messenger RNAs (mRNAs), 142 miRNAs, 990 lncRNAs, and 183 circRNAs were identified as significantly differentially expressed across the four groups. GO and KEGG enrichment analysis revealed the significant roles of GTPase activity and the MAPK signaling pathway in AD pathogenesis. A circRNA-miRNA-lncRNA ceRNA pathway, characterized by the downregulated hsa-miR-7-5p and upregulated hsa_circ_0001170, was identified based on the differentially expressed RNAs between the NC group and the moD group.

Conclusion

The study suggests that circRNAs may be independent of mRNAs in AD pathogenesis and holds promise as potential biomarkers for AD clinical manifestations and pathological changes.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cnr/10.2174/0115672026305417240209062508
2024-03-13
2025-01-24

  • From This Site

    /content/journals/cnr/10.2174/0115672026305417240209062508
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. PrinceM. AliG.C. GuerchetM. PrinaA.M. AlbaneseE. WuY.T. Recent global trends in the prevalence and incidence of dementia, and survival with dementia.Alzheimers Res. Ther.2016812310.1186/s13195‑016‑0188‑8 27473681
     [Google Scholar]
  2. KawasC. GrayS. BrookmeyerR. FozardJ. ZondermanA. Age-specific incidence rates of Alzheimer’s disease.Neurology200054112072207710.1212/WNL.54.11.2072 10851365
     [Google Scholar]
  3. MirraS.S. HeymanA. McKeelD. The consortium to establish a registry for Alzheimer’s Disease (CERAD).Neurology199141447948610.1212/WNL.41.4.479 2011243
     [Google Scholar]
  4. BraakH. AlafuzoffI. ArzbergerT. KretzschmarH. TrediciD.K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry.Acta Neuropathol.2006112438940410.1007/s00401‑006‑0127‑z 16906426
     [Google Scholar]
  5. BraakH. ThalD.R. GhebremedhinE. TrediciD.K. Stages of the pathologic process in Alzheimer disease: Age categories from 1 to 100 years.J. Neuropathol. Exp. Neurol.2011701196096910.1097/NEN.0b013e318232a379 22002422
     [Google Scholar]
  6. JackC.R.Jr BennettD.A. BlennowK. NIA‐AA research framework: Toward a biological definition of Alzheimer’s disease.Alzheimers Dement.201814453556210.1016/j.jalz.2018.02.018 29653606
     [Google Scholar]
  7. DuboisB. VillainN. FrisoniG.B. Clinical diagnosis of Alzheimer’s disease: Recommendations of the international working group.Lancet Neurol.202120648449610.1016/S1474‑4422(21)00066‑1 33933186
     [Google Scholar]
  8. GuerraB.S. LimaJ. AraujoB.H.S. Biogenesis of circular RNAs and their role in cellular and molecular phenotypes of neurological disorders.Semin. Cell Dev. Biol.202111411010.1016/j.semcdb.2020.08.003 32893132
     [Google Scholar]
  9. ZhangY. XueW. LiX. The biogenesis of nascent circular RNAs.Cell Rep.201615361162410.1016/j.celrep.2016.03.058 27068474
     [Google Scholar]
  10. LeiK. BaiH. WeiZ. The mechanism and function of circular RNAs in human diseases.Exp. Cell Res.2018368214715810.1016/j.yexcr.2018.05.002 29730164
     [Google Scholar]
  11. HansenT.B. WiklundE.D. BramsenJ.B. miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA.EMBO J.201130214414442210.1038/emboj.2011.359 21964070
     [Google Scholar]
  12. WestholmJ.O. MiuraP. OlsonS. Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation.Cell Rep.2014951966198010.1016/j.celrep.2014.10.062 25544350
     [Google Scholar]
  13. YouX. VlatkovicI. BabicA. Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity.Nat. Neurosci.201518460361010.1038/nn.3975 25714049
     [Google Scholar]
  14. Rybak-WolfA. StottmeisterC. GlažarP. Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed.Mol. Cell201558587088510.1016/j.molcel.2015.03.027 25921068
     [Google Scholar]
  15. LiangD. TatomerD.C. LuoZ. The output of protein-coding genes shifts to circular RNAs when the Pre-mRNA processing machinery is limiting.Mol. Cell2017685940954.e310.1016/j.molcel.2017.10.034 29174924
     [Google Scholar]
  16. CarlesC.L. IcardoD.O. PorcelM.L. Assessing circular RNAs in Alzheimer’s disease and frontotemporal lobar degeneration.Neurobiol. Aging20209271110.1016/j.neurobiolaging.2020.03.017 32335360
     [Google Scholar]
  17. LiuL. ChenX. ChenY.H. ZhangK. Identification of circular RNA hsa_Circ_0003391 in peripheral blood is potentially associated with Alzheimer’s disease.Front. Aging Neurosci.20201260196510.3389/fnagi.2020.601965 33424579
     [Google Scholar]
  18. BondiM.W. EdmondsE.C. JakA.J. Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and progression rates.J. Alzheimers Dis.201442127528910.3233/JAD‑140276 24844687
     [Google Scholar]
  19. EdmondsE.C. Delano-WoodL. GalaskoD.R. SalmonD.P. BondiM.W. Subtle cognitive decline and biomarker staging in preclinical Alzheimer’s disease.J. Alzheimers Dis.201547123124210.3233/JAD‑150128 26402771
     [Google Scholar]
  20. MinoshimaS. DrzezgaA.E. BarthelH. SNMMI procedure standard/EANM practice guideline for amyloid PET imaging of the brain 1.0.J. Nucl. Med.20165781316132210.2967/jnumed.116.174615 27481605
     [Google Scholar]
  21. DobinA. DavisC.A. SchlesingerF. STAR: Ultrafast universal RNA-seq aligner.Bioinformatics2013291152110.1093/bioinformatics/bts635 23104886
     [Google Scholar]
  22. LiB. DeweyC.N. RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome.BMC Bioinformatics20111232310.1186/1471‑2105‑12‑323
     [Google Scholar]
  23. LangmeadB. TrapnellC. PopM. SalzbergS.L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.Genome Biol.2009103R2510.1186/gb‑2009‑10‑3‑r25 19261174
     [Google Scholar]
  24. FriedländerM.R. MackowiakS.D. LiN. ChenW. RajewskyN. miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades.Nucleic Acids Res.2012401375210.1093/nar/gkr688 21911355
     [Google Scholar]
  25. KozomaraA. JonesG.S. miRBase: Annotating high confidence microRNAs using deep sequencing data.Nucleic Acids Res.201442D1D68D7310.1093/nar/gkt1181
     [Google Scholar]
  26. KozomaraA. BirgaoanuM. JonesG.S. miRBase: From microRNA sequences to function.Nucleic Acids Res.201947D1D155D16210.1093/nar/gky1141
     [Google Scholar]
  27. AguilarB.J. ZhuY. LuQ. Rho GTPases as therapeutic targets in Alzheimer’s disease.Alzheimers Res. Ther.2017919710.1186/s13195‑017‑0320‑4 29246246
     [Google Scholar]
  28. JordanK.L. KossD.J. OuteiroT.F. GiorginiF. Therapeutic targeting of rab GTPases: Relevance for Alzheimer’s disease.Biomedicines2022105114110.3390/biomedicines10051141 35625878
     [Google Scholar]
  29. MusilliM. NicoliaV. BorrelliS. ScarpaS. DianaG. Behavioral effects of Rho GTPase modulation in a model of Alzheimer’s disease.Behav. Brain Res.201323722322910.1016/j.bbr.2012.09.043 23026376
     [Google Scholar]
  30. De FilippisB. ValentiD. ChiodiV. Modulation of Rho GTPases rescues brain mitochondrial dysfunction, cognitive deficits and aberrant synaptic plasticity in female mice modeling Rett syndrome.Eur. Neuropsychopharmacol.201525688990110.1016/j.euroneuro.2015.03.012 25890884
     [Google Scholar]
  31. TanM.S. YangY.X. XuW. Associations of Alzheimer’s disease risk variants with gene expression, amyloidosis, tauopathy, and neurodegeneration.Alzheimers Res. Ther.20211311510.1186/s13195‑020‑00755‑7 33419465
     [Google Scholar]
  32. ArendtT. StielerJ.T. HolzerM. Tau and tauopathies.Brain Res. Bull.2016126Pt 323829210.1016/j.brainresbull.2016.08.018 27615390
     [Google Scholar]
  33. PuigB. Gómez-IslaT. RibéE. Expression of stress‐activated kinases c‐Jun N‐terminal kinase (SAPK/JNK‐P) and p38 kinase (p38‐P), and tau hyperphosphorylation in neurites surrounding βA plaques in APP Tg2576 mice.Neuropathol. Appl. Neurobiol.200430549150210.1111/j.1365‑2990.2004.00569.x 15488025
     [Google Scholar]
  34. TabnerB.J. AgnafE.O.M.A. TurnbullS. Hydrogen peroxide is generated during the very early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and familial British dementia.J. Biol. Chem.200528043357893579210.1074/jbc.C500238200 16141213
     [Google Scholar]
  35. TamagnoE. GuglielmottoM. GilibertoL. JNK and ERK1/2 pathways have a dual opposite effect on the expression of BACE1.Neurobiol. Aging200930101563157310.1016/j.neurobiolaging.2007.12.015 18255190
     [Google Scholar]
  36. LiaoY.F. WangB.J. ChengH.T. KuoL.H. WolfeM.S. Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway.J. Biol. Chem.200427947495234953210.1074/jbc.M402034200 15347683
     [Google Scholar]
  37. DongX. BaiY. LiaoZ. Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease.Nat. Commun.2023141532710.1038/s41467‑023‑40348‑0 37723137
     [Google Scholar]
  38. PuriS. HuJ. SunZ. Identification of circRNAs linked to Alzheimer’s disease and related dementias.Alzheimers Dement.20231983389340510.1002/alz.12960 36795937
     [Google Scholar]
  39. ChenS.D. LuJ.Y. LiH.Q. Staging tau pathology with tau PET in Alzheimer’s disease: A longitudinal study.Transl. Psychiatry202111148310.1038/s41398‑021‑01602‑5 34537810
     [Google Scholar]
  40. DubeU. Del-AguilaJ.L. LiZ. An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations.Nat. Neurosci.201922111903191210.1038/s41593‑019‑0501‑5 31591557
     [Google Scholar]
  41. SuL. WangC. ZhengC. WeiH. SongX. A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson’s disease.BMC Med. Genomics20181114010.1186/s12920‑018‑0357‑7 29653596
     [Google Scholar]
  42. SabaieH. MoghaddamM.M. MoghaddamM.M. Long non-coding RNA-associated competing endogenous RNA axes in the olfactory epithelium in schizophrenia: A bioinformatics analysis.Sci. Rep.20211112449710.1038/s41598‑021‑04326‑0 34969953
     [Google Scholar]
  43. KernF. KrammesL. DanzK. Validation of human microRNA target pathways enables evaluation of target prediction tools.Nucleic Acids Res.202149112714410.1093/nar/gkaa1161 33305319
     [Google Scholar]
  44. LeeM. WooJ. KimS.T. MicroRNA super-resolution imaging in blood for Alzheimer’s disease.BMB Rep.202356319019510.5483/BMBRep.2022‑0151 36404596
     [Google Scholar]
  45. McMillanK.J. MurrayT.K. VergnioryB.N. Loss of MicroRNA-7 regulation leads to α-synuclein accumulation and dopaminergic neuronal loss in vivo.Mol. Ther.201725102404241410.1016/j.ymthe.2017.08.017 28927576
     [Google Scholar]
  46. TwohigD. NielsenH.M. α-synuclein in the pathophysiology of Alzheimer’s disease.Mol. Neurodegener.2019141910.1186/s13024‑019‑0320‑x
     [Google Scholar]
  47. ShimK.H. KangM.J. YounY.C. AnS.S.A. KimS. Alpha-synuclein: A pathological factor with Aβ and tau and biomarker in Alzheimer’s disease.Alzheimers Res. Ther.20221411410.1186/s13195‑022‑01150‑0
     [Google Scholar]
  48. QiuY. HouY. ZhouY. Comprehensive characterization of multi-omic landscapes between gut-microbiota metabolites and the G-protein-coupled receptors in Alzheimer’s disease.bioRxiv202210.1101/2022.09.20.508759
     [Google Scholar]
  49. KambohM.I. Genomics and functional genomics of Alzheimer’s disease.Neurotherapeutics202219115217210.1007/s13311‑021‑01152‑0
     [Google Scholar]
  50. GuL. XuG. LiuD. Poly (adenosine diphosphate ribose) polymerase-1 single nucleotide polymorphism in the 3′-untranslated region for ischemic stroke risk reduction.Curr. Neurovasc. Res.202118330230610.2174/1567202618666210916122553 34530710
     [Google Scholar]
  51. da GalváoF.G. DantasF.F.L. da SilvaE.V. LeonA.S.V. de SouzaJ.M. Association of variants in FCGR2A, PTPN2, and GM-CSF with cerebral cavernous malformation: Potential biomarkers for a symptomatic disease.Curr. Neurovasc. Res.202118217218010.2174/1567202618666210603125630 34082682
     [Google Scholar]
/content/journals/cnr/10.2174/0115672026305417240209062508
Loading
Whole Transcriptome Sequencing of Peripheral Blood Identifies the Alzheimer's Disease-Related circRNA-miRNA-lncRNA Pathway
Curr Neurovasc Res 21, 184 (2024); https://doi.org/10.2174/0115672026305417240209062508
/content/journals/cnr/10.2174/0115672026305417240209062508
/content/journals/cnr/10.2174/0115672026305417240209062508
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): Alzheimer’s dementia; Alzheimer’s disease continuum; circRNA-miRNA-lncRNA; clinical dementia rating; mild cognitive impairment; whole transcriptome sequencing

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test